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Open Access 01-12-2019 | Multiple Sclerosis | Original research

Cessation of anti-VLA-4 therapy in a focal rat model of multiple sclerosis causes an increase in neuroinflammation

Authors: S. K. Vainio, A. M. Dickens, J. Tuisku, O. Eskola, O. Solin, E. Löyttyniemi, D. C. Anthony, J. O. Rinne, L. Airas, M. Haaparanta-Solin

Published in: EJNMMI Research | Issue 1/2019

Abstract

Background

Positron emission tomography (PET) can be used for in vivo evaluation of the pathology associated with multiple sclerosis. We investigated the use of longitudinal PET imaging and the 18-kDa translocator protein (TSPO) binding radioligand [¹⁸F]GE-180 to detect changes in a chronic multiple sclerosis-like focal delayed-type hypersensitivity experimental autoimmune encephalomyelitis (fDTH-EAE) rat model during and after anti-VLA-4 monoclonal antibody (mAb) treatment. Thirty days after lesion activation, fDTH-EAE rats were treated with the anti-VLA-4 mAb (n = 4) or a control mAb (n = 4; 5 mg/kg, every third day, subcutaneously) for 31 days. Animals were imaged with [¹⁸F]GE-180 on days 30, 44, 65, 86 and 142. Another group of animals (n = 4) was used for visualisation the microglia with Iba-1 at day 44 after a 2-week treatment period.

Results

After a 2-week treatment period on day 44, there was a declining trend (p = 0.067) in [¹⁸F]GE-180-binding in the anti-VLA-4 mAb-treated animals versus controls. However, cessation of treatment for 4 days after a 31-day treatment period increased [¹⁸F]GE-180 binding in animals treated with anti-VLA-4 mAb compared to the control group (p = 0.0003). There was no difference between the groups in TSPO binding by day 142.

Conclusions

These results demonstrated that cessation of anti-VLA-4 mAb treatment for 4 days caused a transient rebound increase in neuroinflammation. This highlights the usefulness of serial TSPO imaging in the fDTH-EAE model to better understand the rebound phenomenon.

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Title: Cessation of anti-VLA-4 therapy in a focal rat model of multiple sclerosis causes an increase in neuroinflammation
Authors: S. K. Vainio
A. M. Dickens
J. Tuisku
O. Eskola
O. Solin
E. Löyttyniemi
D. C. Anthony
J. O. Rinne
L. Airas
M. Haaparanta-Solin
Publication date: 01-12-2019
Publisher: Springer Berlin Heidelberg
Keywords: Multiple Sclerosis
Positron Emission Tomography
Published in: EJNMMI Research / Issue 1/2019
Electronic ISSN: 2191-219X
DOI: https://doi.org/10.1186/s13550-019-0508-7

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Cessation of anti-VLA-4 therapy in a focal rat model of multiple sclerosis causes an increase in neuroinflammation

Abstract

Background

Results

Conclusions

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Background

Results

Conclusions

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